Emerging strategies to stop progression and restore function in MS

When I started as a laboratory immunologist more than 20 years ago, the major focus in MS research was searching for ways to turn off the destructive immune attacks. These efforts paid off as there are now immune-based therapies that can help control relapsing forms of disease for many people. While researchers continue to look for ways to improve the treatment of relapsing MS, the focus in MS research is shifting to discovering strategies that stop MS progression and repair the damage that causes disability. This has relevance to people with all types of MS, but especially people with progressive MS.
 
In 2005 the National MS Society made significant investments into nervous system repair and protection research – and we continue to see some promising results. People are excited by the possibility, once only a dream, that we will find a way to repair damaged myelin. This is important not only for restoring  function, but many believe that re-establishing the protective myelin coating on axons will shield them from further harm. As noted neuroscientist Dr. Bruce Trapp said during his presentation, “Remyelination is the best neuroprotective strategy for MS patients.”  
 
Dr. Trapp’s team at Cleveland Clinic and others have been doing a lot of work to advance the field of nervous system repair. They have shown that new MS lesions undergo natural repair much better than older (“chronic”) ones. They’ve also reported that the problem is not a lack of cells capable of making new myelin in these old lesions, but their inability to produce new myelin, and work is now underway to figure out what the impediment is and how to jump-start the repair process.
 
I was intrigued by his work looking at MS lesions that straddle two different parts of the brain – the so-called white matter and the gray matter. The team found that chronic lesions in the white matter (contains a lot of myelin and the lesions can be seen on a standard MRI scan) don’t remyelinate. But chronic lesions in the gray matter (has less myelin and the lesions cannot be seen on an MRI scan), show robust remyelination – even in people living with MS into their 70’s. This opens up opportunities to compare differences in the two regions and figure out how to make the white matter repair like the gray matter. This work is already underway, as shown by a study the Trapp team presented this week at ECTRIMS.
 
Related to this work, Dr. Larry Sherman and colleagues at the Oregon Health and Science University found that fragments of a molecule called hyaluronic acid (HA for short) accumulate in chronic white matter lesions and could be at least partially responsible for the stalled remyelination. They have identified an enzyme that chews up the HA into fragments and have shown that inhibitors of this enzyme promote remyelination. They are now trying to figure out exactly how this works, in hopes of developing treatments that promote remyelination.
 
While originally studied for their anti-inflammatory activity, increasing evidence suggests that female sex hormones might be neuroprotective and/or promote repair of myelin. I saw two very interesting presentations reporting that different estrogen-like molecules could stimulate production of new myelin. Both of these projects are being supported by the Society.
 
Another strategy to repair myelin in MS is to introduce new repair cells into the system via transplantation. Of note was a presentation by investigators from Milan, Italy, who used mouse skin stem cells and forced them to become myelin-making cells. As in previous studies of this type, after these cells were infused into the spinal cord, they promoted recovery in mice with the MS-like disease EAE. The team showed that these cells didn’t actually make myelin themselves, and they’re starting to identify the growth factors they release, which stimulate natural repair and also reduce inflammation. More work is needed, but this type of research gives hope that this strategy may eventually help restore lost function.
 
Updates on two repair therapies already being tested in human clinical trials were also presented this week. The first is called anti-LINGO. LINGO is seen in neurons and myelin-producing oligodendrocytes, and blockading this protein with anti-LINGO has been shown to promote remyelination in animal models. An investigative team from Biogen Idec reported that anti-LINGO was well tolerated in people and that no negative effects were seen in the nervous system using MRI scans. This means the company will likely keep pursuing clinical development of this promising repair candidate.
 
In other exciting news, investigators from the Mayo Clinic are developing an agent called rHIgM22 that has been shown to promote extensive remyelination in several different animal models of MS. This agent is now in early clinical trial testing in MS. 
 
There was a lot of strong work presented at ECTRIMS representing progress in understanding what drives myelin destruction and nerve degeneration in MS, which are key factors underlying progressive forms of the disease. We’re not there yet, but this work holds the promise of uncovering new targets for stopping progression and stimulating repair.
Tags Progressive MS, Research      12 Appreciate this
Bruce

Bruce Bebo, PhD

Bruce Bebo, PhD, is Associate Vice President of Discovery Research at the National MS Society, and was previously a research immunologist focusing on the influence of sex hormones on MS. He is a driven and passionate Society volunteer, successful fundraiser and advocate, fueled in part by the fact that his mother has lived with MS for more than 30 years. 

    63 CommentsReply

  • dave   Oct 6, 2013 11:52 AM
    Thank you
  • Pam   Oct 6, 2013 11:55 AM
    Please do not stop doing what you're doing. Primary Progressive MS diagnosed in May 2008.
  • Amber   Oct 6, 2013 12:04 PM
    I really hope these studies continue and that we are close to a cure. Thank you for your work.
  • Darek Baksik   Oct 6, 2013 12:24 PM
    I love the new evidence, that we are moving forward, in the study of MS. I am 42 Oct. 4th 1971. I plan to go back to work, if this keeps up. GOOD JOB GUYS/GALS! Thank you, and keep on doing what your doing.
  • Ashley   Oct 6, 2013 12:25 PM
    I agree with Pam...I also was diagnosed with PPMS in Dec 2008, and am now in a wheelchair. I would give anything to be able to walk again, and maybe have a relationship where the men do not look at me as "special" and run the other way. Keep up the awesome work that you are doing.
  • Debw1123   Oct 6, 2013 12:29 PM
    Thank you Dr. Bebo.
    The help that you are giving me, ans others like me, is grearly appreciated!
    God Bless You!
  • Dave   Oct 6, 2013 12:31 PM
    Thank you for your determination to find a cure.
  • RAMONA   Oct 6, 2013 12:46 PM
    thank you for further studies, i have ms been blind twice and got my eyesight back, but have suffered numerous mini strokes, still up and going, but know one day that may come to a stand still and look forward to new help
  • Susanbrowe  Oct 6, 2013 12:46 PM
    Dr. Bebo,
    Thank you for being where those of us with multiple sclerosis could not be this past week: in Copenhagen, Denmark absorbing all that researchers have invested in time, money and brain power and trying to learn how to actualize the promise of that black machete--to exterminate once and for all that neurodegenerative disorder represented by those two orange letters, MS.
  • Joan   Oct 6, 2013 12:47 PM
    I was diagnosed 35 years ago....fought hard..now in a wheel chair. I have wonderful support from my husband, family, and friends. Sure hope and pray this leads to a cure soooooon!
  • Joan   Oct 6, 2013 12:47 PM
    I was diagnosed 35 years ago....fought hard..now in a wheel chair. I have wonderful support from my husband, family, and friends. Sure hope and pray this leads to a cure soooooon!
  • Elizabeth Mroz   Oct 6, 2013 1:13 PM
    Thank you for all of your research and dedication. I have Progressive MS and I really appreciate your efforts.
  • Judy Holston   Oct 6, 2013 1:29 PM
    THANK YOU.
  • christine crichton   Oct 6, 2013 1:30 PM
    exciting times ! so positive,thank-you all so much
  • Esther   Oct 6, 2013 1:32 PM
    Thank you and please continue your research. I have been battling MS since I was 25 I am now 61 and getting worse please find a cure. Thanks again.
  • MaryAnn   Oct 6, 2013 1:49 PM
    Thank you.
  • Deli   Oct 6, 2013 1:53 PM
    Good news! I I was diagnosed 13 years ago, ..now Progressive MS and wheel chair... Please don't stop until find a cure.
  • Karen Phillips   Oct 6, 2013 2:07 PM
    Thank you,it gives HOPE !!
  • Shelley   Oct 6, 2013 2:15 PM
    Thank You!! So excited to read this!!
  • Debbie   Oct 6, 2013 2:16 PM
    It does seem like the research is getting close to some answers for MS. Thank you for your commitment to your research. I lost my mom to MS and now my 29 yr old son has it. I am praying that research can help my son asap. It is a horrible disease.
    Thank god for people like you!
  • Lori   Oct 6, 2013 2:16 PM
    This would be a dream come true! I would cry tears of joy if I could walk well again! Thank you for all the information and hard work!
  • Kim   Oct 6, 2013 2:53 PM
    Thank you for giving us all hope, despite what kind of MS we have !!! I pray everyday a cure will be found in time to perhaps cure the next generation if not mine.
  • K2   Oct 6, 2013 3:33 PM
    I know the answer to my question / comment but thank you for the opportunity to voice it:
    With the focus now turning to PPMS why is it still that all clinical trials have to initiate with RRMS? I know that funding is the answer and results sooner than later driving the bus. Those of us with PPMS do not have any therapies available to us and the ones on the horizon have to go through trials with RRMS. Please someone explain to the funding sources that some those of us with PPMS would be more than happy
  • Kathleen   Oct 6, 2013 3:46 PM
    Thank you thank you thank you! 33years of relapsing/remitting and it is now believed I have turned the corner to Secondary Progressive.
    Remyelination is what I have been waiting for years.
    THANK YOU
  • Kathy McGlothlin   Oct 6, 2013 4:03 PM
    Thank you for not giving up on us! RRMS - PPMS all of us need need help and I so appreciate your hard work & dedication.
  • taylorl  Oct 6, 2013 4:16 PM
    The research is fantastic news. I'm 68 and recently diagnosed. I wonder if I will reap the benefits in my lifetime.
  • Kathy DiGesu   Oct 6, 2013 5:32 PM
    My daughter Karen came to live with me 5 years ago (she is now 46). She was using a cane and walking was difficult. In April this year she had a very bad MS attack and is now paralyzed in a nursing home. She is a lovely person and everyone loves her even her nurses. I pray to God everyday for a cure for her. Keep working hard for this cure ! A mom who loves her daughter Kathy DiGesu
  • Judi Seaberg   Oct 6, 2013 5:40 PM
    THANK YOU!!! I'm 56 Yrs. old & have just been Diagnoused w/MS....I think it gets worse daily!!! I am on Betaseron! THANK YOU FOR ALL YOUR HARD WORK and UPDATES~
  • Pam Rombalski   Oct 6, 2013 8:10 PM
    My daughter, 28 years old was just diagnosed with ms about 6 weeks ago. It is hearbreaking as a parent to hear this news. This was not in the plan you have for your child. Thank you so much to everyone who is a part of any research in finding better treatments or a cure. I pray for all of you who have been diagnosed and your families.
  • Kathleen   Oct 6, 2013 8:40 PM
    I pray everyday for a cure & I thank you for all you do. I do believe in a cure.
  • Rina   Oct 6, 2013 8:54 PM
    My daughter was diagnosed at age 14, symptoms starting as early as 11 yrs old. She is now 20 and doing fairly well but not without major flare ups in the past and trying every medication out there finally settling on one that seems to be working, Thank Goodness! As her mom The heartache I feel is unexplainable. Please, lets find a cure in our lifetime. It's a devastating disease and no one should suffer from it. Thank you for all your hard work and dedication to this disease.
  • Rae   Oct 6, 2013 9:54 PM
    I was finally dx'd 3yrs ago. It's so encouraging to read all the studies being done. I hope there's a major breakthrough in my lifetime. I'm 42. Keep the good work!
  • Marcella Kirk   Oct 7, 2013 6:55 AM
    How do we get involved in the stem cell research? Copaxone caused lumps @ injection sites, possible side effects in other drugs sent me to just natural vitamins, cod liver oil B-12,D-3, etc. felt much better until dental & urinary tract infections flared up!
  • Linda Clark   Oct 7, 2013 8:30 AM
    Thank you so much for your research. I have been living with MS for 24 years,I'm one of the lucky ones who is not in a wheelchair,walking on my own,with some difficulty at times. I feel very blessed.
  • Donnaq   Oct 7, 2013 10:32 AM
    This research brings tears of joy to my eyes. Please keep searching for treatments for Progressive MS.
  • Felix Vcente   Oct 7, 2013 12:30 PM
    I would love to volunteer, for test trials I currently don't use any MS meds.
    If there was an opportunity for my gait to return to a somewhat normal state that would be great.
  • Rev. Faith E. Cobb   Oct 8, 2013 3:56 AM
    Thank you for your work; may God be with you to lead you to the fullness of the answers for this very important work. Thank you so much for your dedication. - diagnosed 2009 | suffered from the effects daily since about 2000.
  • fallon   Oct 8, 2013 7:50 AM
    thank you i have been waiting 9 years for this news
  • Nancy Sullivan   Oct 8, 2013 4:09 PM
    Diagnosed with RRMS in 1979. Currently do not work. Participate in a disability committee with members who live in my town. I dream of a cure within my lifetime. Thanks for all of your work!
  • Bernadette   Oct 9, 2013 12:14 AM
    I am grateful for the MS research that s currently underway. Thank you to all the brilliant scientists who are involved with this R &D, and the clinical trials.
  • Karen   Oct 9, 2013 7:16 PM
    God be with all those wonderful people in labs and studies looking for a cure. My dad suffered terribly with ms. My daughter was diagnosed last year. I pray everyday for a cure.
  • Robin Tammens   Oct 10, 2013 4:46 AM
    Hi,
    Diagnosed in 2004 with RRMS and things were steady for a while even after re-diagnosis with PPMS. However, things have been on a steady, ever-increasing decline over the last three years. Drug trial brought hope but no result so now pinning my hopes on all this fantastic new research.
  • Avatar
    kfw718  Oct 12, 2013 5:27 PM
    I was diagnosed three weeks ago and immediately jumped in to researching all the treatments, etc. One of my first questions was: Why do all the medications focus on suppressing our white blood cell count? Why aren't their medications available that will protect and regenerate our myelin? Sure regeneration vs. immune system suppression seemed like a much better path to me. Two weeks in to this line of thinking, several articles have poppoed up about just that. This makes me very hopeful. I am 31, diagnosed with RRMS three weeks ago, however I believe I've been living with the disease since I was 17. The only major "flare up" I've had is optic neuritis, which is what led me to my diagnosis. I feel so hopeful that the new research will help. Right now, I'm signing up for Tecfidera, exercising, eating healthy and urrounding myself with support. It's extremely difficult now knowing how this disease will manifest itself in me (since everyone is so different).
  • Avatar
    kfw718  Oct 12, 2013 5:27 PM
    I was diagnosed three weeks ago and immediately jumped in to researching all the treatments, etc. One of my first questions was: Why do all the medications focus on suppressing our white blood cell count? Why aren't their medications available that will protect and regenerate our myelin? Sure regeneration vs. immune system suppression seemed like a much better path to me. Two weeks in to this line of thinking, several articles have poppoed up about just that. This makes me very hopeful. I am 31, diagnosed with RRMS three weeks ago, however I believe I've been living with the disease since I was 17. The only major "flare up" I've had is optic neuritis, which is what led me to my diagnosis. I feel so hopeful that the new research will help. Right now, I'm signing up for Tecfidera, exercising, eating healthy and urrounding myself with support. It's extremely difficult now knowing how this disease will manifest itself in me (since everyone is so different).
  • Kathi   Oct 17, 2013 10:51 AM
    I can't even find words to express how I feel. I have always believed a cure would be found. While I am grateful for the ability I still have, I am hopeful to be able to walk smoothly and confidently again. Thank you for you efforts.
  • Carol McCoy   Oct 17, 2013 11:08 AM
    This is wonderful, hopeful news especially for people with ppms which I have been dealing with for 20 yrs. Thanks so much for brightening my day!
  • Chris   Oct 17, 2013 12:16 PM
    My daughter was diagnosed in 2011. She is 21 now and doing well on copaxone thank God. This is good news. Please keep pushing hard for a cure for this terrible disease. I don’t want another family to have to go through what we are going through.
  • Jerry   Oct 17, 2013 1:34 PM
    I was dx'd in 2002 with spms went into a wheelchair in2005. I would be willing to subject myself to clinical trials if it will help cure this disease! Thx for all the hard work. God Bless you
  • Amy   Oct 17, 2013 2:10 PM
    I was diagnosed RRMS in 2005 with lots of lesions and both my MS and disability curve progressed rapidly. By the time I hit upon a disease-modifying drug that worked for me, it was a challenge to find a clean slice in my MRI films and I had a great deal of disability, visible and invisible. For me, Tysabri stopped the progression in its tracks, but there's still all the pre-existing lesions, some of them in dangerous places.
    A couple years ago, some years old lesions in and around my hypothalamus disappeared from my MRI. (Before I knew that, I noticed a positive change in symptoms related to blood pressure and urge to urinate.) I don't mean to contradict the researchers -- it was a strange enough thing that my neuro (who just does MS and is one of the best for it in the country if not the world) raised an eyebrow over it. He said, "it happens..." but I was left with the impression that it happens very rarely else he wouldn't have expressed surprise. Perhaps it's so uncommon that the researchers' samples weren't large enough to notice.
    If the standard line is still that old white matter lesions don't repair, I wonder what the difference is between me and most MSers. Is it something intrinsic to me and the presumably tiny percentage like me? Is it something about the location of the lesions (in that, afaik, only my midbrain lesions have shown such signs)? By symptom lists, it seems midbrain lesions are very uncommon in MS, so perhaps only some of that small percentage would have old lesions that greatly improve. Is it something about rapid progression that responds very well to treatment? If (and I don't know this) the brain only has limited myelin-repairing resources and it nearly always focuses on the most recent damage, then every time there's new damage, it'd abandon whatever it was repairing before completion. Maybe if there are no more fires, the repair crew can go back and finish up the work. Could even be a combination of formerly fast progressing MS and the lesion location, that the repair crew would only go back to finish fixing the most vital of areas. These are only laymens' hypotheses, some guesses that seem reasonable on relatively little knowledge. But if old white matter lesions don't heal--except some of them do for few people--I wonder if anyone's interested in investigating this.
  • Chrystiana Sailer   Oct 17, 2013 2:29 PM
    It is not a matter of IF something will be found to stop, slow, reverse MS it is a matter of When and because of dedicated hard working Doctors, researchers, scientists like you - it is getting closer. Mahalo!
  • Avatar
    joanhuntley  Oct 17, 2013 3:21 PM
    Thank you for all you efforts, I was diagnosed in June/2013 RRMS, at 61. I wonder how mant years I have been battling this disease. I have just finished my 3/4 dose and next week will be my first full dose of Avonex! I have such hope in your efforts.
  • Debbie   Oct 17, 2013 5:47 PM
    I have had RRMS since 1996. I was 28 years old. I was diagnosed fast and started Betaseron. It worked well but I want to try something new that is not an injection. I will start taking Tecfidera soon! I am lucking I still work with only small to average exacerbations every three years with approx 90-95% repair. I have decreased my working hours but I am happy and lucky to be able to work, walk, drive and care for myself and enjoy my family. My wonderful husband helps and is very receptive to me and the desease process.This is wonderful news and Thank You for Your hard work! I have been waiting for a cure for 18 years and like all of these people it gives all of us HOPE!
  • steven   Oct 17, 2013 7:05 PM
    Patients, please check out also the awesome work being done by the Myelin Repair Foundation and support them if you can. They're on track to having a myelin repair drug to us by 2019
  • Vincent Spoto   Oct 17, 2013 8:13 PM
    It is so exciting to learn that research being done is now increasingly more focused on function restoration through myelin regeneration. I'm optimistic and remain confident that by the end of this decade, 2020, a major breakthrough will be made relating to MS restoration of function and damage repair. In the meantime, I encourage everyone to have a positive attitude, stay active and EXCERCISE regularly! We need to keep our bodies strong so that when 2020 comes, we are ready and can welcome in the New Year in style!

    Thanks to all the scientists, researchers and neurologists for keeping a steady foot on the 'gas' and steering us into a future world that is free of MS!

    Vincent Spoto - Secondary Progressive
    Diagnosed with RRMS in 2006
  • Cristen   Oct 17, 2013 10:36 PM
    I participated in the Lingo study in Centennial, Colorado. I was with the very first group. We were all so very excited. I have now been considered for the second phase, which, according to my father who is a Wall Street analyst, should take off soon. Biogen announced the new drug which raised their stock $7.00 a share. This means they are moving forward and I get to be part in the second phase!
  • KLF   Oct 18, 2013 7:14 AM
    I'm glad to see chronic/progressive MS getting more attention, In the past, I was dismayed that RRMS was always mentioned but not CPMS. Don't get me wrong, I hope RRMS is cured. But I'm glad CPMS is being addressed.
  • JL   Oct 18, 2013 10:00 PM
    I just wanted to thank you and all the researchers working on our behalf! Hope is so powerful and we all have our reasons to want to get better. I have a wonderful family, supportive husband and daughter and a son with autism that I need to be around to help in future years. I don't want to be a burden to any of them and I want to help my husband with our later life and taking care of our son, not be an additional stress in his life. Your work is so important and I just wanted you to know how grateful I am to have brilliant researchers working towards goals that will change my future. Please keep up the mission and thank you so much! :)
  • Joanne   Oct 28, 2013 5:25 PM
    Even though I still have the flu like symptoms from my medicine I'm still very thankful that I can swing dance, go bowling with my friends and do aerobics 3 to 4 times a week. Keep up the good work and hopefully some day you will stop the progression in its tracks for good. God Bless diagnosed in 2006
  • Pamela   Oct 31, 2013 9:17 AM
    Thank you, Dr. Bebo, for your continued research on MS. My has had this evil disease for about 13 or 14 years. She has lost control of all body parts, except her head, which is slowly losing control of as well. She is losing hope. I call her, to let her know about the research being done, and tell her to keep her faith that something great will happen. She takes Copaxone once a day, but it's not helping her regain the use of anything. Even if she does not walk again, I think she will be ecstatic to be able to control her upper extremities. So please keep up the great work. Let's find a cure!
  • Pamela   Oct 31, 2013 9:20 AM
    *my aunt...
  • Anita Schneider   Dec 7, 2013 11:36 PM
    I was diagnosed with RRMS n 2011. I am 59 years old Thank you for all yur work to find a cure for this disease. I take Copaxone and can still walk holding on to doors and furniture but it sees to be getting worse and sometimes I just want to lay in bed because it makes me relax. I exercise regularly but sometimes I get so upset because I never had such a debilitating disease like this and I appreciate all of your efforts to end this and I pray daily for a cure.
  • hchunter  Dec 17, 2013 6:54 PM
    Frankly, I'd be afraid to leave my treatment of betaseron as I've been on it for 11 years, and it has worked. Yes, I'd like the simplicity of a pill, but would be scared to put my health at risk.
  • Mary Brown-Doehle   Dec 19, 2013 5:25 PM
    Thank you for working on MS. My son was diagonised 21/2 years ago and we now know he has had it longer. He is only 37 and this disease has had its toll on him already. Please find a cure.